Recently, a novel type of potential anticancer agent has been developed [Koyama, Kelly and Watanabe, U.S. Ser. No. 302,836, filed Jan. 27, 1989] now U.S. Pat. No. 4,966,918 which contains both intercalating and alkylating capabilities. Chrysophanol (1A, FIG. 1) and emodin (1B) were converted into 3-[N,N-bis(2-chloroethyl)-amino]methyl-1,8-dihydroxy-9,10-anthraquinone (3A) and its 6-methoxy analog (3B) via the respective 1,8-dimethoxy intermediates (2A and 2B). The natural products, 1A and 1B, may have the intercalating capability but lack the alkylating function, whereas 2A and 2B may have the alkylating capability but are incapable of intercalating into DNA due to the presence of two bulky methoxy groups. These compounds are practically inactive against mouse leukemic cells L1210 in tissue culture. However, 3A and 3B which contain both intercalating and alkylating capabilities exhibited potent inhibitory activity against L1210 cells in tissue culture.
A recent publication [Koyama, Kelly and Watanabe, J. Med. Chem., 31:283-284 (1988)], showed that planar molecules with basic nature can interact with DNA more strongly than the neutral species. On the basis of the above considerations and discoveries, the present invention was developed.